Confinement and catalysis within de novo designed peptide barrels

Rokas Petrenas, Olivia A. Hawkins, Jacob F. Jones, D. Arne Scott, Jordan M. Fletcher, Ulrike Obst, Lucia Lombardi, Fabio Pirro, Graham J. Leggett, Thomas A.A. Oliver*, Derek N. Woolfson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

De novo protein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities. To address this, here we describe the design, characterization, and application of small-molecule:peptide ternary complexes in aqueous solution. This uses α-helical barrel (αHB) peptide assemblies, which comprise 5 or more α helices arranged around central channels. These channels are solvent accessible, and their internal dimensions and chemistries can be altered predictably. Thus, αHBs are analogous to “molecular flasks” made in supramolecular, polymer, and materials chemistry. Using Förster resonance energy transfer as a readout, we demonstrate that specific αHBs can accept two different organic dyes, 1,6-diphenyl-1,3,5-hexatriene and Nile red, in close proximity. In addition, two anthracene molecules can be accommodated within an αHB to promote anthracene photodimerization. However, not all ternary complexes are productive, either in energy transfer or photodimerization, illustrating the control that can be exerted by judicious choice and design of the αHB.

Original languageEnglish
Pages (from-to)3796–3803
JournalJournal of the American Chemical Society
Volume147
Issue number4
Early online date15 Jan 2025
DOIs
Publication statusPublished - 29 Jan 2025
Externally publishedYes

Keywords

  • peptide barrels
  • Confinement
  • catalysis

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

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